Expression of galanin (GAL, a 30-amino acid peptide) gene occurs in hypothalamic gonadotropin-releasing hormone (GnRH) neurons in rodent brain. This expression of GAL mRNA increases during the preovulatory surge secretion of luteinizing hormone (LH) when GnRH release is also elevated. Moreover, both the GAL antagonist, galantide, and antiserum against GAL suppress pulsatile release of LH in ovariectomized (OVX) rats and the preovulatory LH surge in ovarian-intact individuals. This evidence suggests that GAL may stimulate neuronal GnRH release. In pig-tailed macaques GAL mRNA in hypothalamic neurons is enhanced by estrogen (E) stimulation, although expression of this GAL mRNA is not colocalized in the same neurons with GnRH according to Dr. Robert Steiner and colleagues at the University of Washington. Their laboratory in Seattle and ours in Portland have initiated a collaborative study to determine if intrahypothalamic infusion of GAL stimulates GnRH release in OVX-E-treated macaques. Six rhesus macaques were OVX and immediately implanted with a 3-cm Silastic capsule containing crystalline E to maintain blood E levels between 30 to 90 pg/ml, i.e., follicular phase E levels. Subsequently, these monkeys received push-pull cannulae (PPC) directed into the median eminence (ME) of the hypothalamus. Push-pull perfusion (PPP) was performed for 9 h with GAL (80 fM) being introduced continuously into the ME via the PPC during h6 to h8. In the last hour (h9), neuropeptide Y (NPY), which is known to stimulate GnRH release, was given via the PPC to serve as a positive control. The results suggest that GAL administered locally into the ME did not alter ME-GnRH release whereas NPY increased GnRH levels in PPP samples by 50-100%. These GnRH data indicate that intrahypothalamic GAL infusion fails to alter GnRH release. Other observations from the Seattle group suggests intravenous injection of GAL can stimulate a modest rise in serum LH. Collectively, these data suggest that GAL acts either on the pituitary gland per se or on target cells in the brain that are beyond reach of the infusate.